Expanded HIV-1 Cellular Tropism by Phenotypic Mixing with Murine Endogenous Retroviruses

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Abstract
In view of the current interest in in vivo murine models for acquired immunodeficiency syndrome (AIDS), the interaction between human immunodeficiency virus type 1 (HIV-1) and endogenous murine leukemia virus (MuLV)-related retroviruses was investigated with a human leukemic T cell line (PF-382 x ) that acquired xenotropic MuLV (X-MuLV) after in vivo passage in immunosuppressed mice. Despite similar levels of membrane CD4 expression and HIV-1 125 I-labeled gp120 binding, a dramatic acceleration in the time course of HIV-1 infection was observed in PF-382 x compared to its X-MuLV-negative counterpart (PF-382). Moreover, PF-382 cells coinfected by X-MuLV and HIV-1 generated a progeny of phenotypically mixed viral particles, enabling HIV-1 to productively infect a panel of CD4 - human cells, including B lymphoid cells and purified normal peripheral blood CD4 - /CD8 + T lymphocytes. Mixed viral phenotypes were also produced by human CD4 + T cells coinfected with an amphotropic MuLV-related retrovirus (A-MuLV) and HIV-1. These data show that endogenous MuLV acquired by human cells transplanted into mice can significantly interact with HIV-1, thereby inducing important alterations of HIV-1 biological properties.